背景:小肠复发性出血占消化道出血病例的5%至10%,仍然是治疗挑战。沙利度胺已被评估用于治疗由于小肠血管发育不良(SIA)引起的复发性出血,但缺乏确证试验。
方法:我们进行了多中心,双盲,随机化,安慰剂对照试验研究沙利度胺治疗SIA所致复发性出血的疗效和安全性.因SIA导致的复发性出血(前一年至少有四次出血)的符合条件的患者被随机分配接受口服每日剂量为100mg或50mg的沙利度胺或安慰剂,为期4个月。在4个月治疗期结束后,对患者进行至少1年的随访。主要终点是有效反应,定义为与治疗前一年相比,沙利度胺治疗结束后一年内发生的出血事件数量减少至少50%。关键次要终点是停止出血而不再出血。输血,因为出血住院,出血持续时间,和血红蛋白水平。
结果:总体而言,150例患者接受随机分组:51例进入100-mg沙利度胺组,50mg沙利度胺组49,安慰剂组50。100mg沙利度胺组有效反应的患者百分比,50毫克沙利度胺组,安慰剂组为68.6%,51.0%,和16.0%,分别(三组同时比较P<0.001)。次要终点的分析结果支持主要终点的分析结果。与安慰剂组相比,沙利度胺组的不良事件更常见;具体事件包括便秘,嗜睡,肢体麻木,外周水肿,头晕,和肝脏酶水平升高。
结论:在这项安慰剂对照试验中,沙利度胺治疗可减少因SIA引起的复发性出血患者的出血.(由国家自然科学基金委员会和上海市教委资助,高峰临床医学;临床试验。gov编号,NCT02707484。).
BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal
angiodysplasia (SIA), but confirmatory trials are lacking.
METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels.
RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels.
CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of
China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).